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Article ; Online: More than Just a Monolayer: the Multifaceted Role of Endothelial Cells in the Pathophysiology of Atherosclerosis.

Mussbacher, Marion / Schossleitner, Klaudia / Kral-Pointner, Julia B / Salzmann, Manuel / Schrammel, Astrid / Schmid, Johannes A

Current atherosclerosis reports

2022 Volume 24, Issue 6, Page(s) 483–492

Abstract: Purpose of the review: In this review, we summarize current insights into the versatile roles of endothelial cells in atherogenesis.: Recent findings: The vascular endothelium represents the first barrier that prevents the entry of lipoproteins and ... ...

Abstract	Purpose of the review: In this review, we summarize current insights into the versatile roles of endothelial cells in atherogenesis. Recent findings: The vascular endothelium represents the first barrier that prevents the entry of lipoproteins and leukocytes into the vessel wall, thereby controlling two key events in the pathogenesis of atherosclerosis. Disturbance of endothelial homeostasis increases vascular permeability, inflammation, and cellular trans-differentiation, which not only promotes the build-up of atherosclerotic plaques but is also involved in life-threatening thromboembolic complications such as plaque rupture and erosion. In this review, we focus on recent findings on endothelial lipoprotein transport, inflammation, cellular transitions, and barrier function. By using cutting-edge technologies such as single-cell sequencing, epigenetics, and cell fate mapping, novel regulatory mechanisms and endothelial cell phenotypes have been discovered, which have not only challenged established concepts of endothelial activation, but have also led to a different view of the disease.
MeSH term(s)	Atherosclerosis/etiology ; Endothelial Cells ; Endothelium, Vascular ; Humans ; Inflammation/complications ; Plaque, Atherosclerotic/complications
Language	English
Publishing date	2022-04-11
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2057369-8
ISSN	1534-6242 ; 1523-3804
ISSN (online)	1534-6242
ISSN	1523-3804
DOI	10.1007/s11883-022-01023-9
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Article: PI3K Isoform Signalling in Platelets.

Schrottmaier, Waltraud C / Mussbacher, Marion / Salzmann, Manuel / Kral-Pointner, Julia B / Assinger, Alice

Current topics in microbiology and immunology

2022 Volume 436, Page(s) 255–285

Abstract: Platelets are unique anucleated blood cells that constantly patrol the vasculature to seal and prevent injuries in a process termed haemostasis. Thereby they rapidly adhere to the subendothelial matrix and recruit further platelets, resulting in platelet ...

Abstract	Platelets are unique anucleated blood cells that constantly patrol the vasculature to seal and prevent injuries in a process termed haemostasis. Thereby they rapidly adhere to the subendothelial matrix and recruit further platelets, resulting in platelet aggregates. Apart from their central role in haemostasis, they also kept some of their features inherited by their evolutionary ancestor-the haemocyte, which was also involved in immune defences. Together with leukocytes, platelets fight pathogenic invaders and guide many immune processes. In addition, they rely on several signalling pathways which are also relevant to immune cells. Among these, one of the central signalling hubs is the PI3K pathway. Signalling processes in platelets are unique as they lack a nucleus and therefore transcriptional regulation is absent. As a result, PI3K subclasses fulfil distinct roles in platelets compared to other cells. In contrast to leukocytes, the central PI3K subclass in platelet signalling is PI3K class Iβ, which underlines the uniqueness of this cell type and opens new ways for potential platelet-specific pharmacologic inhibition. An overview of platelet function and signalling with emphasis on PI3K subclasses and their respective inhibitors is given in this chapter.
MeSH term(s)	Blood Platelets/metabolism ; Blood Platelets/pathology ; Hemostasis/physiology ; Humans ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Isoforms/metabolism ; Thrombosis/metabolism ; Thrombosis/pathology
Chemical Substances	Protein Isoforms
Language	English
Publishing date	2022-10-15
Publishing country	Germany
Document type	Journal Article
ISSN	0070-217X
ISSN	0070-217X
DOI	10.1007/978-3-031-06566-8_11
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Article ; Online: Platelet-leukocyte interplay during vascular disease.

Schrottmaier, Waltraud C / Mussbacher, Marion / Salzmann, Manuel / Assinger, Alice

Atherosclerosis

2020 Volume 307, Page(s) 109–120

Abstract: Vascular disease is a progressive inflammatory condition fuelled by an unhealthy lifestyle of physical inactivity, cholesterol-rich diet, and smoking. Together with endogenous factors such as age, gender, and autoimmune status, an unhealthy lifestyle ... ...

Abstract	Vascular disease is a progressive inflammatory condition fuelled by an unhealthy lifestyle of physical inactivity, cholesterol-rich diet, and smoking. Together with endogenous factors such as age, gender, and autoimmune status, an unhealthy lifestyle fosters a pro-inflammatory and pro-thrombotic milieu, which can lead to endothelial dysfunction, atherosclerotic plaque formation and vascular obstruction or degradation of the subendothelial matrix. Platelet-leukocyte interplay represents an important feature in this context. Platelets get activated in a pro-inflammatory and pro-thrombotic microenvironment and readily interact with innate and adaptive immune cells alike. Even though platelet affinity for physical cell-cell contact is highest with monocytes/macrophages and neutrophils, platelets also avidly interact with lymphocytes by soluble mediators. Platelet-leukocyte crosstalk regulates essential immune responses, supporting leukocyte recruitment at sites of vascular insult, promoting proliferation and differentiation of leukocytes and enhancing pro-inflammatory effector functions such as cytokine and reactive oxygen production. However, under certain conditions platelet-leukocyte interplay also dampens the inflammatory process. Crosstalk of platelet and leukocytes thus represents a driving force in vascular disease. In this review, we highlight the impact of various risk factors for vascular disease on platelet-leukocyte interactions and discuss the underlying mechanisms of platelet-mediated changes in immune responses and the effect of immune cells on the haemostatic system. As the underlying pathologies differ between vascular diseases, we summarize our current knowledge on platelet-leukocyte interplay in chronic vascular diseases such as abdominal aortic aneurysm, peripheral and coronary artery disease as well as acute vascular diseases such as ischaemic stroke and venous thromboembolism.
MeSH term(s)	Blood Platelets ; Brain Ischemia ; Humans ; Inflammation ; Leukocytes ; Neutrophils ; Stroke
Language	English
Publishing date	2020-05-11
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80061-2
ISSN	1879-1484 ; 0021-9150
ISSN (online)	1879-1484
ISSN	0021-9150
DOI	10.1016/j.atherosclerosis.2020.04.018
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Article ; Online: Reduced Monocyte and Neutrophil Infiltration and Activation by P-Selectin/CD62P Inhibition Enhances Thrombus Resolution in Mice.

Kral-Pointner, Julia B / Haider, Patrick / Szabo, Petra L / Salzmann, Manuel / Brekalo, Mira / Schneider, Karl H / Schrottmaier, Waltraud C / Kaun, Christoph / Bleichert, Sonja / Kiss, Attila / Sickha, Romana / Hengstenberg, Christian / Huber, Kurt / Brostjan, Christine / Bergmeister, Helga / Assinger, Alice / Podesser, Bruno K / Wojta, Johann / Hohensinner, Philipp

Arteriosclerosis, thrombosis, and vascular biology

2024 Volume 44, Issue 4, Page(s) 954–968

Abstract: Background: Venous thromboembolism is a major health problem. After thrombus formation, its resolution is essential to re-establish blood flow, which is crucially mediated by infiltrating neutrophils and monocytes in concert with activated platelets and ...

Abstract	Background: Venous thromboembolism is a major health problem. After thrombus formation, its resolution is essential to re-establish blood flow, which is crucially mediated by infiltrating neutrophils and monocytes in concert with activated platelets and endothelial cells. Thus, we aimed to modulate leukocyte function during thrombus resolution post-thrombus formation by blocking P-selectin/CD62P-mediated cell interactions. Methods: Thrombosis was induced by inferior vena cava stenosis through ligation in mice. After 1 day, a P-selectin-blocking antibody or isotype control was administered and thrombus composition and resolution were analyzed. Results: Localizing neutrophils and macrophages in thrombotic lesions of wild-type mice revealed that these cells enter the thrombus and vessel wall from the caudal end. Neutrophils were predominantly present 1 day and monocytes/macrophages 3 days after vessel ligation. Blocking P-selectin reduced circulating platelet-neutrophil and platelet-Ly6C Conclusions: Inhibition of P-selectin-dependent activation of monocytes and neutrophils accelerates venous thrombosis resolution due to reduced infiltration and activation of innate immune cells at the site of thrombus formation, which prevents early thrombus stabilization and facilitates fibrinolysis.
MeSH term(s)	Mice ; Humans ; Animals ; Monocytes/pathology ; P-Selectin ; Endothelial Cells ; Thromboplastin ; Neutrophil Infiltration ; Thrombosis ; Neutrophils
Chemical Substances	P-Selectin ; Thromboplastin (9035-58-9)
Language	English
Publishing date	2024-02-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.123.320016
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Zs.A 1705: Show issues

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Article ; Online: Quantitative and Functional Assessment of the Influence of Routinely Used Cryopreservation Media on Mononuclear Leukocytes for Medical Research.

Haider, Patrick / Hoberstorfer, Timothy / Salzmann, Manuel / Fischer, Michael B / Speidl, Walter S / Wojta, Johann / Hohensinner, Philipp J

International journal of molecular sciences

2022 Volume 23, Issue 3

Abstract: Quantitative and functional analysis of mononuclear leukocyte populations is an invaluable tool to understand the role of the immune system in the pathogenesis of a disease. Cryopreservation of mononuclear cells (MNCs) is routinely used to guarantee ... ...

Abstract	Quantitative and functional analysis of mononuclear leukocyte populations is an invaluable tool to understand the role of the immune system in the pathogenesis of a disease. Cryopreservation of mononuclear cells (MNCs) is routinely used to guarantee similar experimental conditions. Immune cells react differently to cryopreservation, and populations and functions of immune cells change during the process of freeze-thawing. To allow for a setup that preserves cell number and function optimally, we tested four different cryopreservation media. MNCs from 15 human individuals were analyzed. Before freezing and after thawing, the distribution of leukocytes was quantified by flow cytometry. Cultured cells were stimulated using lipopolysaccharide, and their immune response was quantified by flow cytometry, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA). Ultimately, the performance of the cryopreservation media was ranked. Cell recovery and viability were different between the media. Cryopreservation led to changes in the relative number of monocytes, T cells, B cells, and their subsets. The inflammatory response of MNCs was altered by cryopreservation, enhancing the basal production of inflammatory cytokines. Different cryopreservation media induce biases, which needs to be considered when designing a study relying on cryopreservation. Here, we provide an overview of four different cryopreservation media for choosing the optimal medium for a specific task.
MeSH term(s)	Cell Culture Techniques/methods ; Cell Survival ; Cells, Cultured ; Cryopreservation/methods ; Female ; Flow Cytometry ; Humans ; Leukocyte Count ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/metabolism ; Male
Language	English
Publishing date	2022-02-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23031881
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Article ; Online: Platelets in Sepsis: An Update on Experimental Models and Clinical Data.

Assinger, Alice / Schrottmaier, Waltraud C / Salzmann, Manuel / Rayes, Julie

Frontiers in immunology

2019 Volume 10, Page(s) 1687

Abstract: Beyond their important role in hemostasis, platelets play a crucial role in inflammatory diseases. This becomes apparent during sepsis, where platelet count and activation correlate with disease outcome and survival. Sepsis is caused by a dysregulated ... ...

Abstract	Beyond their important role in hemostasis, platelets play a crucial role in inflammatory diseases. This becomes apparent during sepsis, where platelet count and activation correlate with disease outcome and survival. Sepsis is caused by a dysregulated host response to infection, leading to organ dysfunction, permanent disabilities, or death. During sepsis, tissue injury results from the concomitant uncontrolled activation of the complement, coagulation, and inflammatory systems as well as platelet dysfunction. The balance between the systemic inflammatory response syndrome (SIRS) and the compensatory anti-inflammatory response (CARS) regulates sepsis outcome. Persistent thrombocytopenia is considered as an independent risk factor of mortality in sepsis, although it is still unclear whether the drop in platelet count is the cause or the consequence of sepsis severity. The role of platelets in sepsis development and progression was addressed in different experimental
MeSH term(s)	Animals ; Blood Coagulation/physiology ; Blood Platelets/pathology ; Hemostasis/physiology ; Humans ; Inflammation/pathology ; Models, Theoretical ; Sepsis/pathology
Language	English
Publishing date	2019-07-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2019.01687
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Article ; Online: Correlation between MRI-based spinal muscle parameters and the vertebral bone quality score in lumbar fusion patients.

Moser, Manuel / Albertini Sanchez, Leonardo / Adl Amini, Dominik / Oezel, Lisa / Salzmann, Stephan N / Muellner, Maximilian / Haffer, Henryk / Tan, Ek T / Shue, Jennifer / Sama, Andrew A / Cammisa, Frank P / Girardi, Federico P / Hughes, Alexander P

Brain & spine

2023 Volume 3, Page(s) 102684

Abstract: Introduction: The vertebral bone quality (VBQ) score that is based on non-contrast enhanced T1-weighted MRI was recently introduced as a novel measure of bone quality in the lumbar spine and shown to be a significant predictor of healthy versus ... ...

Abstract	Introduction: The vertebral bone quality (VBQ) score that is based on non-contrast enhanced T1-weighted MRI was recently introduced as a novel measure of bone quality in the lumbar spine and shown to be a significant predictor of healthy versus osteopenic/osteoporotic bone. Research question: This study aimed to assess possible correlations between the VBQ score and the functional cross-sectional area (FCSA) of psoas and lumbar spine extensor muscles. Material and methods: Patients who underwent fusion surgery between 2014 and 2017 and had lumbar MRI and CT scans within 6 months prior to surgery were included. The FCSA was assessed at L3-L5 using a pixel intensity threshold method. The VBQ score was calculated by dividing the signal intensity (SI) of the vertebrae L1-L4 through the SI of the cerebrospinal fluid at L3. Volumetric bone mineral density (vBMD) was assessed by quantitative CT. Results: 80 patients (58.8% female, median age 68.8 years) were included. Overall prevalence of osteopenia/osteoporosis was 66.3%, with no significant differences between men and women. The mean (SD) VBQ score was significantly smaller in men, at 2.26 (0.45) versus women at 2.59 (0.39) ( Conclusion: Our results highlight sex differences in the VBQ score that were not demonstrated by vBMD and suggest a potential role of this novel measure to assess not only bone quality, but also spinal muscle quantity.
Language	English
Publishing date	2023-09-30
Publishing country	Netherlands
Document type	Journal Article
ISSN	2772-5294
ISSN (online)	2772-5294
DOI	10.1016/j.bas.2023.102684
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Article ; Online: Short-term toll-like receptor 9 inhibition leads to left ventricular wall thinning after myocardial infarction.

Lenz, Max / Kiss, Attila / Haider, Patrick / Salzmann, Manuel / Brekalo, Mira / Krychtiuk, Konstantin A / Hamza, Ouafa / Huber, Kurt / Hengstenberg, Christian / Podesser, Bruno K / Wojta, Johann / Hohensinner, Philipp J / Speidl, Walter S

ESC heart failure

2023 Volume 10, Issue 4, Page(s) 2375–2385

Abstract: Aims: Ischaemia-reperfusion injury (IRI) following myocardial infarction remains a challenging topic in acute cardiac care and consecutively arising heart failure represents a severe long-term consequence. The extent of neutrophil infiltration and ... ...

Abstract	Aims: Ischaemia-reperfusion injury (IRI) following myocardial infarction remains a challenging topic in acute cardiac care and consecutively arising heart failure represents a severe long-term consequence. The extent of neutrophil infiltration and neutrophil-mediated cellular damage are thought to be aggravating factors enhancing primary tissue injury. Toll-like receptor 9 was found to be involved in neutrophil activation as well as chemotaxis and may represent a target in modulating IRI, aspects we aimed to illuminate by pharmacological inhibition of the receptor. Methods and results: Forty-nine male adult Sprague-Dawley rats were used. IRI was induced by occlusion of the left coronary artery and subsequent snare removal after 30 min. Oligonucleotide (ODN) 2088, a toll-like receptor 9 (TLR9) antagonist, control-ODN, or DNase, were administered at the time of reperfusion and over 24 h via a mini-osmotic pump. The hearts were harvested 24 h or 4 weeks after left coronary artery occlusion and immunohistochemical staining was performed. Echocardiography was done after 1 and 4 weeks to determine ventricular function. Inhibition of TLR9 by ODN 2088 led to left ventricular wall thinning (P = 0.003) in association with drastically enhanced neutrophil infiltration (P = 0.005) and increased markers of tissue damage. Additionally, an up-regulation of the chemotactic receptor CXCR2 (P = 0.046) was found after TLR9 inhibition. No such effects were observed in control-ODN or DNase-treated animals. We did not observe changes in monocyte content or subset distribution, hinting towards neutrophils as the primary mediators of the exerted tissue injury. Conclusions: Our data indicate a TLR9-dependent, negative regulation of neutrophil infiltration. Blockage of TLR9 appears to prevent the down-regulation of CXCR2, followed by an uncontrolled migration of neutrophils towards the area of infarction and the exertion of disproportional tissue injury resulting in potential aneurysm formation. In comparison with previous studies conducted in TLR
MeSH term(s)	Rats ; Mice ; Male ; Animals ; Toll-Like Receptor 9/therapeutic use ; Rats, Sprague-Dawley ; Myocardial Infarction/drug therapy ; Heart ; Coronary Vessels
Chemical Substances	Toll-Like Receptor 9
Language	English
Publishing date	2023-05-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2814355-3
ISSN	2055-5822 ; 2055-5822
ISSN (online)	2055-5822
ISSN	2055-5822
DOI	10.1002/ehf2.14403
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Article ; Online: MRI-based vertebral bone quality score compared to quantitative computed tomography bone mineral density in patients undergoing cervical spinal surgery.

Oezel, Lisa / Okano, Ichiro / Jones, Conor / Salzmann, Stephan N / Shue, Jennifer / Adl Amini, Dominik / Moser, Manuel / Chiapparelli, Erika / Sama, Andrew A / Carrino, John A / Cammisa, Frank P / Girardi, Federico P / Hughes, Alexander P

European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society

2023 Volume 32, Issue 5, Page(s) 1636–1643

Abstract: Purpose: The vertebral bone quality (VBQ) score based on magnetic resonance imaging (MRI) was introduced as a bone quality marker in the lumbar spine. Prior studies showed that it could be utilized as a predictor of osteoporotic fracture or ... ...

Abstract	Purpose: The vertebral bone quality (VBQ) score based on magnetic resonance imaging (MRI) was introduced as a bone quality marker in the lumbar spine. Prior studies showed that it could be utilized as a predictor of osteoporotic fracture or complications after instrumented spine surgery. The objective of this study was to evaluate the correlation between VBQ scores and bone mineral density (BMD) measured by quantitative computer tomography (QCT) in the cervical spine. Methods: Preoperative cervical CT and sagittal T1-weighted MRIs from patients undergoing ACDF were retrospectively reviewed and included. The VBQ score in each cervical level was calculated by dividing the signal intensity of the vertebral body by the signal intensity of the cerebrospinal fluid on midsagittal T1-weighted MRI images and correlated with QCT measurements of the C2-T1 vertebral bodies. A total of 102 patients (37.3% female) were included. Results: VBQ values of C2-T1 vertebrae strongly correlated with each other. C2 showed the highest VBQ value [Median (range) 2.33 (1.33, 4.23)] and T1 showed the lowest VBQ value [Median (range) 1.64 (0.81, 3.88)]. There was significant weak to moderate negative correlations between and VBQ Scores for all levels [C2: p < 0.001; C3: p < 0.001; C4: p < 0.001; C5: p < 0.004; C6: p < 0.001; C7: p < 0.025; T1: p < 0.001]. Conclusion: Our results indicate that cervical VBQ scores may be insufficient in the estimation of BMDs, which might limit their clinical application. Additional studies are recommended to determine the utility of VBQ and QCT BMD to evaluate their potential use as bone status markers.
MeSH term(s)	Humans ; Female ; Male ; Bone Density ; Retrospective Studies ; Tomography, X-Ray Computed/methods ; Magnetic Resonance Imaging ; Cervical Vertebrae/diagnostic imaging ; Cervical Vertebrae/surgery ; Lumbar Vertebrae
Language	English
Publishing date	2023-03-07
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1115375-1
ISSN	1432-0932 ; 0940-6719
ISSN (online)	1432-0932
ISSN	0940-6719
DOI	10.1007/s00586-023-07570-2
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Zs.A 3437: Show issues

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Article ; Online: Neutrophil extracellular traps induce persistent lung tissue damage via thromboinflammation without altering virus resolution in a mouse coronavirus model.

Salzmann, Manuel / Gibler, Patrizia / Haider, Patrick / Brekalo, Mira / Plasenzotti, Roberto / Filip, Thomas / Nistelberger, Rebecca / Hartmann, Boris / Wojta, Johann / Hengstenberg, Christian / Podesser, Bruno K / Kral-Pointner, Julia B / Hohensinner, Philipp J

Journal of thrombosis and haemostasis : JTH

2023 Volume 22, Issue 1, Page(s) 188–198

Abstract: Background: During infection, neutrophil extracellular traps (NETs) are associated with severity of pulmonary diseases such as acute respiratory disease syndrome. NETs induce subsequent immune responses, are directly cytotoxic to pulmonary cells, and ... ...

Abstract	Background: During infection, neutrophil extracellular traps (NETs) are associated with severity of pulmonary diseases such as acute respiratory disease syndrome. NETs induce subsequent immune responses, are directly cytotoxic to pulmonary cells, and are highly procoagulant. Anticoagulation treatment was shown to reduce in-hospital mortality, indicating thromboinflammatory complications. However, data are sparsely available on the involvement of NETs in secondary events after virus clearance, which can lead to persistent lung damage and postacute sequelae with chronic fatigue and dyspnea. Objectives: This study focuses on late-phase events using a murine model of viral lung infection with postacute sequelae after virus resolution. Methods: C57BL/6JRj mice were infected intranasally with the betacoronavirus murine coronavirus (MCoV, strain MHV-A95), and tissue samples were collected after 2, 4, and 10 days. For NET modulation, mice were pretreated with OM-85 or GSK484 and DNase I were administered intraperitoneally between days 2 to 5 and days 4 to 7, respectively. Results: Rapid, platelet-attributed thrombus formation was followed by a second, late phase of thromboinflammation. This phase was characterized by negligible virus titers but pronounced tissue damage, apoptosis, oxidative DNA damage, and presence of NETs. Inhibition of NETs during the acute phase did not impact virus burden but decreased lung cell apoptosis by 67% and oxidative stress by 94%. Prevention of neutrophil activation by immune training before virus infection reduced damage by 75%, NETs by 31%, and pulmonary thrombi by 93%. Conclusion: NETs are detrimental inducers of tissue damage during respiratory virus infection but do not contribute to virus clearance.
MeSH term(s)	Animals ; Mice ; Extracellular Traps ; Neutrophils ; Coronavirus ; Thromboinflammation ; Disease Models, Animal ; Inflammation/complications ; Thrombosis/complications ; Mice, Inbred C57BL ; Lung ; Coronavirus Infections/complications
Language	English
Publishing date	2023-09-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1016/j.jtha.2023.09.014
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